Robot-assisted laparoscopic radical cystectomy with intracorporeal ileal conduit diversion versus open radical cystectomy with ileal conduit for bladder cancer in an ERAS setup (BORARC): protocol for a single-centre, double-blinded, randomised feasibility study.

BACKGROUND: Radical cystectomy (RC) with urinary diversion is the recommended treatment for selected cases of non-metastatic high-risk non-muscle-invasive and muscle-invasive bladder cancer. It remains unknown whether robot-assisted laparoscopic cystectomy (RARC) offers any advantage in terms of safety compared to open cystectomy (ORC) in an Enhanced Recovery After Surgery (ERAS) setup. Blinded randomised controlled trials (RCTs) between RARC versus ORC have never been conducted in cystectomy patients. We will investigate the feasibility of conducting a double-blinded RCT comparing ORC with RARC with intra-corporal ileal conduit (iRARC) in an ERAS setup. METHODS: This is a single-centre, double-blinded, randomised (1:1) clinical feasibility study for patients with non-metastatic high-risk non-muscle-invasive or muscle-invasive bladder cancer scheduled for cystectomy. All participants are recruited from Rigshospitalet, Denmark. The planned sample size is 50 participants to investigate whether blinding of the surgical technique is feasible. Participants and postoperative caring physicians and nurses are blinded using a pre-study designed abdominal dressing and blinding of the patient's electronic health record. Study endpoints are assessed 90 days postoperatively. The primary aim is to study the frequency and pattern of unplanned unblinding after surgery and the number of participants who cannot guess the surgical technique at the day of discharge. Eleven secondary endpoints are assessed: length of stay, days alive and out of hospital, in-hospital complication rate, 30-day complication rate, 90-day complication rate, readmission rate, quality of life, blood loss, pain, rate of moderate/severe post-anaesthesia care unit (PACU) complications, and delirium. Participants are managed in an ERAS setup in both arms of the trial. DISCUSSION: We report on the design and objectives of a novel experimental feasibility study investigating whether blinding of the surgical technique in cystectomy patients is possible. This information is essential for the design of future blinded trials comparing ORC to RARC. There is a continued need to compare RARC and ORC in terms of both efficacy, safety, and oncological outcomes. Estimated end of study is March 2021. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03977831. Registered on the 6th of June 2019.

Quality of life and secondary outcomes for open versus robot-assisted radical cystectomy: a double-blinded, randomised feasibility trial.

PURPOSE: This study aims to examine quality of life (QoL) before and after radical cystectomy (RC) and compare robot-assisted laparoscopy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). METHODS: This study is a predefined secondary analysis of a single-centre, double-blinded, randomised feasibility trial. Fifty patients were randomly assigned to iRARC with ileal conduit (n = 25) or ORC with ileal conduit (n = 25). Patients were followed 90 days postoperatively. The primary outcome was patient-reported QoL using the EORTC Cancer-30 and muscle-invasive bladder cancer BLM-30 QoL questionnaires before and after RC. Differences between randomisation arms as well as changes over time were evaluated. Secondary outcomes included 30- and 90 day complication rates, 90 day readmission rates, and 90 day days-alive-and-out-of-hospital and their relationship to QoL. RESULTS: All patients underwent the allocated treatment. We found no difference in QoL, complication rates, readmission rates, and days-alive-and-out-of-hospital between randomisation arms. An overall improvement in QoL was found in the following domains: future perspectives, emotional functioning, and social functioning. Sexual functioning worsened postoperatively. There was no association between having experienced a major complication or lengthy hospitalisation and worse postoperative QoL. CONCLUSION: The QoL does not appear to depend on surgical technique. Apart from sexual functioning, patients report stable or improved QoL within the first 90 postoperative days.

Effect of a Smoking and Alcohol Cessation Intervention Initiated Shortly Before Radical Cystectomy-the STOP-OP Study: A Randomised Clinical Trial.

BACKGROUND: Evidence concerning the reduction of postoperative complications due to smoking and alcohol drinking in patients undergoing radical cystectomy is incomplete. OBJECTIVE: To evaluate the efficacy of a 6-wk smoking and/or alcohol cessation intervention, initiated shortly before surgery and continued until 4 wk after, in reducing complications. DESIGN, SETTING, AND PARTICIPANTS: Between 2014 and 2018, we enrolled 104 patients with high-risk bladder cancer who were daily smokers or consuming at least 3 units of alcohol daily in a multicentre randomised clinical trial. INTERVENTION: Patients were randomised to a 6-wk intensive smoking and/or alcohol cessation intervention or treatment as usual. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the number of patients developing any postoperative complication, or death, within 30 d after surgery. The secondary endpoints were successful quitters, health-related quality of life, length of stay, time back to habitual activity, and mortality. An intention-to-treat analysis was applied to evaluate treatment effect. RESULTS AND LIMITATIONS: There were some differences in baseline demographic and lifestyle characteristics. Postoperatively, 64% in the intervention group versus 70% in the control group (risk ratio [RR] 0.91, confidence interval [CI] 0.68-1.21, p = 0.51) developed complications. Significantly fewer patients developed three or more complications after 30 d (RR 0.39; CI 0.18-0.84, p = 0.01). The rates of successful quitting were 51% in the intervention group and 27% in the control group (RR 2, CI 1.14-3.51, p = 0.01). The external validity of this trial may be limited because 53% of eligible patients refused participation. CONCLUSIONS: Despite a significant effect on the quit rate at completion of the intervention, this multimodal prehabilitation did not show a significant difference regarding our primary outcome postoperative complications. PATIENT SUMMARY: A 6-wk smoking and alcohol cessation intervention in relation to bladder cancer surgery did not reduce postoperative complications, but it was effective in supporting people to quit in the short term.

Risk of recurrence and long-term mortality following radical cystectomy for bladder cancer.

PURPOSE: To investigate the risk of recurrence and long-term mortality after radical cystectomy (RC) for bladder cancer (BC) at a high-volume tertiary referral center in Denmark over 19 years. MATERIALS AND METHODS: Patients undergoing RC between the 1st of January 2000 to 31st of December 2018 were included. Patient data were manually retrieved from electronic patient files. Follow-up ended 18th of May 2020. Cumulative incidences were used to assess risk of recurrence and mortality using competing risk modelling. Cause-specific Cox regression models were used for multivariable analysis. RESULTS: A total of 1267 patients underwent RC of which 1042 were eligible for analysis. Overall mortality was 40% and 56% after 5 and 10 years, respectively. The cumulative incidence of recurrence and BC specific mortality was high within the first 2 years. Only 3.2% of the patients with recurrence were alive at the end of follow-up. The cumulative incidence of BC mortality after 5 years was 6.7% (95% CI 3.6-9.9) and 10% (95% CI 6.8-14) for patients with ≤ pT1bN0 and pT2N0, respectively. For patients with lymph node positive disease the cumulative incidence of BC mortality after 5 years was 65% (95% CI 58-71). CONCLUSIONS: We found a significant risk of recurrence and disease-specific mortality following RC for BC, especially within the first 2 years following surgery. Our data seem comparable to other large cohorts. The chance of long-term survival following recurrence is low and there is a continuous need to improve adjuvant or salvage strategies following RC.

Long-Term Renal Function Following Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To evaluate long-term renal function following radical cystectomy (RC) for bladder cancer and identify risk factors associated with postoperative decline in renal function. METHODS: The study included patients who underwent RC at a single centre in Denmark between 2009 and 2019. Data was collected through national electronic medical records. Renal function was evaluated by estimated glomerular filtration rate (eGFR) using pre- and postoperative creatinine measurements. Cumulative incidence and Cox Proportional Hazards models were used to describe the loss of renal function and its association with clinicopathological variables, as well as its effect on mortality. RESULTS: After exclusions, 670 patients were eligible for analyses. Median follow-up time was 6.2 years (interquartile range 4.0 -8.4). The proportion of patients with renal insufficiency (eGFR<45 mL/min) increased from 8.9% before RC to 19% 5 years after surgery. A total of 610 patients with preoperative eGFR≥45 were included in survival analyses. The absolute risk of renal function decline to CKD stage G3b or worse (eGFR<45 mL/min) was 17% (95% CI 14 -20) at 5 years postoperatively. Loss of renal function was not significantly associated with higher all-cause mortality. In multivariate analysis lower preoperative eGFR, diabetes mellitus, prior pelvic radiation therapy, continent urinary diversion types, and postoperative ureteral stricture were all independently associated with renal function decline. CONCLUSION: The long-term renal function decreases considerably for a large number of RC patients. Recognizing preoperative risk factors could identify patients who benefit from enhanced renal surveillance or early intervention for modifiable factors to minimize renal insufficiency following RC.

Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study.

OBJECTIVE: To examine surgical outcomes and feasibility of blinding patients and care providers to the surgical technique of radical cystectomy (RC). PATIENTS AND METHODS: Single-centre, parallel-group, double-blinded, randomised feasibility study of open RC (ORC) vs robot-assisted RC with intracorporeal urinary diversion (iRARC) in an 'Enhanced Recovery After Surgery' setup. A total of 50 patients aged ≥18 years with bladder cancer planned for RC with an ileal conduit were included. Patients with previous major abdominal/pelvic surgery, pelvic radiation or anaesthesiological contraindications were excluded. Primary outcomes were proportion of unblinded patients and success of blinding using Bang's Blinding Index. Secondary outcomes included length of stay (LOS), complication rates, blood loss, pain, and opioid consumption. RESULTS: A total of 26% of the patients were unblinded before discharge. We demonstrated that patients and doctors remained blinded for the allocated treatment, but nurses did not. Blood loss was greater in the ORC group as was operative time in the iRARC group. We found no difference in complication rate, LOS, or use of analgesics. CONCLUSIONS: The present study demonstrates that blinding of surgical technique in RC is possible. The results of secondary outcomes are consistent with the findings of previous unblinded randomised controlled trials. Our study highlights that it is possible to perform a blinded phase III study to explore the optimal surgical technique in RC.

Morbidity and Days Alive and Out of Hospital Within 90 Days Following Radical Cystectomy for Bladder Cancer.

BACKGROUND: Morbidity after radical cystectomy (RC) is usually quantified in terms of rates of complications, mortality, reoperations, and readmissions, and length of stay (LOS). The overall burden following RC within the first 90 d following RC may be better described using days alive and out of hospital (DAOH), which is a validated, patient-centred proxy for both morbidity and mortality. OBJECTIVE: To report short-term morbidity, LOS, and DAOH within 90 d after RC and risk factors associated with these parameters. DESIGN SETTING AND PARTICIPANTS: The study included 729 patients undergoing RC for bladder cancer at a single academic centre from 2009 to 2019. Data were retrieved from national electronic medical charts. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate analysis was used to investigate variables associated with a major complication, LOS >7 d, and DAOH <80 d. RESULTS AND LIMITATIONS: The 90-d complication rate was 80%, including major complications in 37% of cases. Median LOS was 7 d (interquartile range (IQR) 6-9) and median DAOH was 80 d (IQR 71-83) days. Body mass index and the Charlson comorbidity index (CCI) predicted major complications. CCI predicted LOS >7 d and DAOH <80 d. CONCLUSIONS: RC was associated with significant short-term morbidity and DAOH was a good marker for cumulative morbidity after RC. We propose that DAOH should be a standard supplement for reporting surgical outcomes following RC for bladder cancer, which may facilitate better comparison of outcomes across treating institutions. PATIENT SUMMARY: We studied complications after surgical removal of the bladder for bladder cancer. We assessed a novel patient-centred tool that more accurately describes the total burden of complications after surgery than traditional models. We found that patients with a high body mass index and coexisting chronic diseases had a higher risk of a complicated surgical course.

Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder.

Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with urothelial carcinoma. The different uPAR forms in blood are strong prognostic markers in other cancer types. We investigate the presence of different uPAR forms in tumour tissue and test the hypothesis that preoperative plasma levels of the uPAR forms predict recurrence free survival, cancer specific survival, and overall survival in patients treated with cystectomy for urothelial carcinoma. Using Western blotting we analyse neoplasia and adjacent benign-appearing urothelium from randomly selected patients for the presence of intact and cleaved uPAR forms. Prospectively collected preoperative plasma samples from 107 patients who underwent radical cystectomy for urothelial carcinoma are analysed. The different uPAR forms are measured by time-resolved fluorescence immunoassays. uPAR in tumour tissue from patients with urothelial carcinoma is demonstrated in both an intact and cleaved form. The different uPAR forms in plasma are all significantly associated with both recurrence free survival, cancer specific survival, and overall survival, high concentrations predicting short survival. uPAR (I) has the strongest association with a HR of 2.56 for overall survival. In the multivariable survival analysis uPAR (I) is significantly associated with cancer specific survival and overall survival.

Oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in Denmark.

Objective: To report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large study sample.Materials and methods: This was a nationwide multicenter registry-based cohort study of all patients with upper urinary tract urothelial neoplasia in Denmark found to be eligible for nephroureterectomy between April 2004 and April 2017 (N = 1384). Primary endpoints were intravesical recurrence-free survival and overall survival. Survival probabilities were estimated with Kaplan-Meier and the log-rank test to compare survival curves. Association with clinical outcomes was studied using univariate and multivariate Cox proportional hazards.Results: Intravesical recurrence-free survival was 72% [95% confidence interval (CI) 69-75%] at 5 years and 70% (95% CI 67-73%) at 10 years. Patients with muscle-invasive disease had a significantly lower rate of intravesical recurrence [hazard ratio (HR) = 0.46, p < 0.0001] and patients with high-grade tumors had a significantly higher rate of incident intravesical recurrence compared to low-grade tumors (HR = 1.65, p = 0.001). The overall survival was 76% (95% CI 74-79%) at 5 years and 64% (95% CI 60-70%) at 10 years. Patients with higher age (p = 0.008) and muscle-invasive disease (p < 0.0001) had worse overall survival. When comparing surgical approaches, laparoscopic nephroureterectomy versus open nephroureterectomy did not differ in intravesical recurrence-free survival but was associated with shorter postoperative hospital stay (p < 0.0001) and better overall survival (p = 0.02).Conclusions: We report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large sample and give insights into predictive factors with significant impact.

Reasons why not all Danish patients with muscle invasive bladder cancer receive neoadjuvant chemotherapy before radical cystectomy.

Background: Danish guidelines on muscle invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC) for non-metastatic patients fit for cisplatin-based chemotherapy. The current indication is urothelial MIBC in patients less than 75 years old with no metastasis on imaging and normal renal function (GFR ≥ 60 ml/min). Data from the Danish Bladder Cancer Database (DaBlaCa-Data) reveals that only 40-50% of MIBC patients below 75 years of age receive NAC prior to cystectomy. The aim of this study was to clarify the reasons why the remaining patients do not receive NAC.Methods: Individual patient data were collected retrospectively from all five Danish urologic departments performing cystectomies. Patients fulfilling the inclusion criteria: MIBC at TURBT, age less than 75 years old and subsequent cystectomy were included and registered by the specific reason why NAC was not given. In total, 449 patients met the age- and T-stage criteria for NAC in the period September 2014 through August 2017.Results: In total, 274 patients (61.0%) received chemotherapy. Of the 175 patients who did not receive NAC, 140 patients (80%) were not fit for cisplatin and 35 patients did not receive NAC and had no specific contraindication. This ranged from 0-18% of included patients in the different centres. The main reason was patient refusal (97%). Interestingly, this ranged from 0-50% of patients not receiving NAC when comparing the five centres.Conclusion: These findings underline the need for proper patient information in order to get a uniform treatment strategy between centres.

Human papillomavirus and squamous cell carcinoma of the urinary bladder: DaBlaCa-10 study.

OBJECTIVE: To evaluate a potential association between Human Papillomavirus (H.P.V.) and squamous cell carcinoma (S.C.C.) urinary bladder cancer (B.C.). Furthermore, the relation between p16INK4a, H.P.V. and B.C. was examined. PATIENTS AND METHODS: Patients were included and divided into three groups based on the histological diagnosis of B.C. SPECIMENS: An extensive exclusion was performed, including accepted casual risk factors for S.C.C. B.C., such as long-term use of catheters, cystolithiasis and Schistosoma hematobium infection. A total of 100 patients were included: 50 with pure S.C.C., 25 with urothelial carcinomas (U.C.) and 25 with squamous differentiation of U.C. (Sq.D.). The patients were operated at one of four major Danish hospitals in the period January 2005 to December 2016. Clinical information was collected from the medical records. Presence of H.P.V. was analyzed using the INNO-LiPA H.P.V. Genotyping Extra II. p16INK4a was analyzed using immunohistochemical (I.H.C.) staining. A p-value <0.05 was considered statistically significant. RESULTS: An overall H.P.V. prevalence of 12/100 (12%) was observed. H.P.V. was demonstrated in 9/50 (18%) of the S.C.C. PATIENTS: Overall, p16INK4a over-expression was observed in 52/100 (52%) patients. However, concomitant H.P.V. positivity and p16INK4a over-expression were observed in only 4/100 (4%) patients. CONCLUSION: The presence of H.P.V. in one fifth of patients with S.C.C. B.C. was demonstrated. H.P.V. infection could have a significant association with S.C.C. B.C. without other known casual risk factors for S.C.C. B.C.

Complications and health-related quality of life after robot-assisted versus open radical cystectomy: a systematic review and meta-analysis of four RCTs.

BACKGROUND: Radical cystectomy is associated with high rates of perioperative morbidity. Robotic-assisted radical cystectomy (RARC) is widely used today despite limited evidence for clinical superiority. The aim of this review was to evaluate the effect of RARC compared to open radical cystectomy (ORC) on complications and secondary on length of stay, time back to work and health-related quality of life (HRQoL). METHODS: The databases PubMed, The Cochrane Library, Embase and CINAHL were searched. A systematic review according to the PRISMA guidelines and cumulative analysis was conducted. Randomized controlled trials (RCTs) that examined RARC compared to ORC were included in this review. We assessed the quality of evidence using the Cochrane Collaboration's 'Risk of bias' tool and Grading of Recommendations Assessment, Development and Evaluation approach. Data were extracted and analysed. RESULTS: The search retrieved 273 articles. Four RCTs were included involving overall 239 patients. The quality of the evidence was of low to moderate quality. There was no significant difference between RARC and ORC in the number of patients developing complications within 30 or 90 days postoperatively or in overall grade 3-5 complications within 30 or 90 days postoperatively. Types of complications differed between the RARC and the ORC group. Likewise, length of stay and HRQoL at 3 and 6 months did not differ. CONCLUSION: Our review presents evidence for RARC not being superior to ORC regarding complications, LOS and HRQoL. High-quality studies with consistent registration of complications and patient-related outcomes are warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016038232.

STOP smoking and alcohol drinking before OPeration for bladder cancer (the STOP-OP study), perioperative smoking and alcohol cessation intervention in relation to radical cystectomy: study protocol for a randomised controlled trial.

BACKGROUND: To evaluate the effect of a smoking-, alcohol- or combined-cessation intervention starting shortly before surgery and lasting 6 weeks on overall complications after radical cystectomy. Secondary objectives are to examine the effect on types and grades of complications, smoking cessation and alcohol cessation, length of hospital stay, health-related quality of life and return to work or habitual level of activity up to 12 months postoperatively. METHODS/DESIGN: The study is a multi-institutional randomised clinical trial involving 110 patients with a risky alcohol intake and daily smoking who are scheduled for radical cystectomy. Patients will be randomised to the 6-week Gold Standard Programme (GSP) or treatment as usual (control). The GSP combines patient education and pharmacologic strategies. Smoking and alcohol intake is biochemically validated (blood, urine and breath tests) at the weekly meetings and at follow-up. DISCUSSION: Herein, we report the design of the STOP-OP study, objectives and accrual up-date. This study will provide new knowledge about how to prevent smoking and alcohol-related postoperative complications at the time of bladder cancer surgery. Till now 77 patients have been enrolled. Patient accrual is expected to be finalised before the end of 2017 and data will be published in 2018. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02188446 . Registered on 28 May 2014.

The Danish Bladder Cancer Database.

AIM OF DATABASE: The aim of the Danish Bladder Cancer Database (DaBlaCa-data) is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC) in Denmark. STUDY POPULATION: All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. MAIN VARIABLES: In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47%) patients were diagnosed with non-muscle-invasive BC (non-MIBC) and 512 (53%) were diagnosed with muscle-invasive BC (MIBC). A total of 300 (31%) patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50%) received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. DESCRIPTIVE DATA: One-year mortality was 28% (95% confidence interval [CI]: 15-21). One-year cancer-specific mortality was 25% (95% CI: 22-27%). One-year mortality after cystectomy was 14% (95% CI: 10-18). Ninety-day mortality after cystectomy was 3% (95% CI: 1-5) in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24-39) and 1-year cancer-specific mortality was 23% (95% CI: 16-31) in 2013. CONCLUSION: This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and monitor treatment and mortality. In the future, DaBlaCa-data will be a valuable data source and expansive observational studies on BC will be available.

Local involvement of the lower urinary tract in primary colorectal cancer - outcome after en-bloc resection.

UNLABELLED: Invasion of urinary organs due to advanced colorectal cancer can comprise a surgical challenge in achieving negative resection margins. The aim of the study was to asses the outcome of patients with colorectal cancer invading the lower urinary organs. MATERIAL AND METHODS: This is a cohort study that retrospectively evaluated the surgical and pathological findings after the resection of colorectal cancer with adjacent urological organs due to advanced colorectal cancer. Patients with primary colorectal cancer invading urological organs where primary resection was attempted were included. RESULTS: The study included 31 patients who underwent surgery in our department between 1997 and 2012. Median age was 65 years (range 44-77 years). Seventeen patients underwent partial cystectomy, one had partial prostatectomy performed, eight patients underwent cystoprostatectomy, two had cystectomy performed and three had prostatectomy performed. Overall morbidity rate was 71% (95% Confidence Interval (CI): 55-84%, n=22). The 30-day mortality rate was 10% (95% CI: 0-23%, n=3). Twentyseven of 31 patients had free resection margins. Four of 28 patients developed distant metastasis (14%, 95% CI: 4-29%), 11% developed local recurrence (95% CI: 0-25%, n=3). Median follow-up was 41 months (range 0-150 months). Histopathological examination revealed tumour invasion in 52% (95% CI: 35-69%, n=15) of the resected urological organs. The overall five-year survival rate was 70%. The five-year survival rate in the radical resection group was 74%. CONCLUSIONS: En-bloc resection of colorectal cancer with adjacent urological organs has a high morbidity rate. However it is still possible to achieve negative resection margins in most cases.

uPAR Expression Pattern in Patients with Urothelial Carcinoma of the Bladder--Possible Clinical Implications.

The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling during cancer invasion and metastasis and is an established prognostic marker in various cancer diseases other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue blocks from 186 patients treated with radical cystectomy were analysed. uPAR expression was scored as either negative or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated by Immunohistochemistry as well as a significant association between uPAR positivity and increasing tumour stage and tumour grade. This demonstrates the robustness of our previous and current findings. In addition the association between uPAR positive myofibroblasts and poor survival was reproduced. The highest hazard ratios for survival were seen for uPAR positive myofibroblasts both at the invasive front and in tumour core. Evaluating uPAR expression by the actual score showed a significant association between uPAR positive myofibroblasts in tumour core and an increased risk of cancer specific mortality. Our investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system.

Retropubic cartilaginous cyst presenting as stress urinary incontinence.

A pubic cartilaginous cyst is a rare condition and is considered a result of degenerative changes in the symphysis pubis, mainly described in elderly multiparous women. There are only a few reported cases in the literature, and patients presented most frequently with a painful vaginal/vulvar mass. This case report is the first to describe a patient with rapidly progressing stress urinary incontinence (SUI) due to a retropubic cartilaginous cyst. The patient in this case underwent surgical intervention; symptoms improved postoperatively, suggesting that surgical intervention in symptomatic patients should be taken into consideration, as it can have beneficial effects. Knowledge of this condition and presenting symptoms is important in order to suggest appropriate management in this rare group of patients.

Urostomy and health-related quality of life in patients with lower urinary tract dysfunction.

OBJECTIVE: Urinary diversion may be an option in patients with disabling lower urinary tract dysfunction (DLUTD), refractory to conservative and minor invasive treatment. The aim of this study was to evaluate whether urostomy improves quality of life and cost of surgery, in terms of complications, loss of kidney function and hospital stay, in these patients. MATERIAL AND METHODS: This prospective study included 52 consecutive patients (nine men and 43 women) with various benign disorders. Twenty-six patients received an ileal conduit and 26 a continent cutaneous diversion. The patients completed the general health-related quality of life instrument WHOQOL-BREF and a urinary problem-specific quality of life instrument preoperatively and 6 and 12 months after surgery. Length of hospital stay and complications were registered. Intravenous urography and determination of glomerular filtration rate (GFR) were performed preoperatively and 12 months postoperatively. RESULTS: Disease-specific and health-related quality of life improved significantly (p < 0.0005 and p < 0.05) in all domains except for social relationship, from preoperative to 12 months after surgery. There was no difference in improvement between patients with continent and those with incontinent diversion. Mean hospital stay was 14 days. Early and late complications required open surgery in 12 patients (23%). GFR was unchanged postoperatively. CONCLUSIONS: Urinary diversion improves health-related and disease-specific quality of life in patients with DLUTD refractory to conservative and minor invasive treatments. The burden of surgery is acceptable. Urinary diversion could be recommended more often in such patients.

[Urethral cancer is rare and difficult to diagnose]. / Uretral cancer er sjælden og vanskelig at diagnosticere.

Primary cancer of the urethra is a rare condition with symptoms ranging from haematuria, urethral obstruction and pelvic pain to urethrocutaneous fistula and abscess. Magnetic resonance imaging (MRI) is considered first choice of diagnostic imaging, but experience with treatment is scarce. We present a case of a 69-year-old woman with a one-year history of urinary obstruction. MRI revealed a tumour surrounding the urethra, and biopsies showed adenocarcinoma in situ. Surgery with removal of the bladder, urethra, internal genitals and lymph nodes revealed a periurethral cyst with both adenocarcinoma in situ and focal adenocarcinoma.

Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial.

OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16 patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P < 0.001) and blinded evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range 0.5 to 2.4) L in the patients who received HES 130/0.4 or lactated Ringer, respectively (P < 0.038). The patients in the lactated Ringer's group, however, received more fluid (P < 0.0001) than those in the HES 130/0.4 group. There was no significant difference between the 2 groups with regard to frequency of reoperations or the length of hospital stay, but use of HES 130/0.4 was both more expensive and less efficacious than the use of lactated Ringer. CONCLUSIONS: Administration of HES 130/0.4 reduced clot strength and perioperative hemorrhage increased by more than 50%, while administration of lactated Ringer's solution provoked an approximately 2.5 times greater positive volume balance at the end of surgery.